1. Technical Field of the Invention
The present invention relates to the therapeutic administration, in particular in the dermatology field, of novel biphenyl compounds substituted with an aromatic radical having selective activity for the gamma subtype of the RAR receptor family.
2. Description of Background and/or Related and/or Prior Art
A family of biphenyl compounds has been described in WO 99/10308. These compounds are described as having an application in the topical and systemic treatment of dermatological conditions linked to a keratinization disorder, and of ophthalmological conditions in particular.
The activity of these compounds has in particular been demonstrated by means of tests for differentiation of mouse embryonic teratocarcinoma F9 cells and keratinocyte differentiation tests in humans.
On the other hand, this publication in no way makes any reference to a possible specific activity of the compounds with respect to the gamma subtype of RAR receptors.
Indeed, the gamma subtype of the RAR receptor family is largely predominant in the epidermis, where it represents approximately 90% of the total receptors (“Retinoic acid receptors and binding proteins in human skin”, Elder J T, Astrom A, Pettersson U, Tavakkol A, Krust A, Kastner P, Chambon P, Voorhees J. J.: J. Invest. Dermatol., 1992; 98 (6 Suppl): 36S-41S; or “Retinoic acid receptor expression in human skin keratinocytes and dermal fibroblasts in vitro”, Redfern C P, Todd C. J. Cell Sci., 1992; 102 (Pt 1): 113-21), and it is indeed the interaction with this RAR gamma receptor which is responsible for the effectiveness of retinoids on the epidermis (“Retinoic acid receptor gamma mediates topical retinoid efficacy and irritation in animal models”, Chen S, Ostrowski J, Whiting G, Roalsvig T, Hammer L, Currier S J, Honeyman J, Kwasniewski B, Yu K L, Sterzycki R, et al., J. Invest. Dermatol., 1995; 104 (5): 779-83).
RAR gamma receptors are therefore the sole target in the treatment of pathologies at the epidermal level, for instance for acne or psoriasis or any other skin pathology treated with retinoids.
Furthermore, certain side effects specific to RAR alpha or RAR beta can be avoided if compounds having a selective action on RAR gamma are used.